Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)
Abstract Carcinoma of Unknown Primary (CUP) is a heterogeneous and metastatic disease where the primary site of origin is undetectable. Currently, chemotherapy is the only state-of-art treatment option for CUP patients. The molecular profiling of the tumour, particularly mutation detection, offers a...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-07-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-94678-4 |
| _version_ | 1818570459023671296 |
|---|---|
| author | Hamidreza Aboulkheyr Es Hamid Mahdizadeh Amir Abbas Hedayati Asl Mehdi Totonchi |
| author_facet | Hamidreza Aboulkheyr Es Hamid Mahdizadeh Amir Abbas Hedayati Asl Mehdi Totonchi |
| author_sort | Hamidreza Aboulkheyr Es |
| collection | DOAJ |
| description | Abstract Carcinoma of Unknown Primary (CUP) is a heterogeneous and metastatic disease where the primary site of origin is undetectable. Currently, chemotherapy is the only state-of-art treatment option for CUP patients. The molecular profiling of the tumour, particularly mutation detection, offers a new treatment approach for CUP in a personalized fashion using targeted agents. We analyzed the mutation and copy number alterations profile of 1709 CUP samples deposited in the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) cohort and explored potentially druggable mutations. We identified 52 significant mutated genes (SMGs) among CUP samples, in which 13 (25%) of SMGs were potentially targetable with either drugs are approved for the know primary tumour or undergoing clinical trials. The most variants detected were TP53 (43%), KRAS (19.90%), KMT2D (12.60%), and CDKN2A (10.30%). Additionally, using pan-cancer analysis, we found similar variants of TERT promoter in CUP and NSCLC samples, suggesting that these mutations may serve as a diagnostic marker for identifying the primary tumour in CUP. Taken together, the mutation profiling analysis of the CUP tumours may open a new way of identifying druggable targets and consequently administrating appropriate treatment in a personalized manner. |
| first_indexed | 2024-12-14T13:41:35Z |
| format | Article |
| id | doaj.art-f1fe39e7ef8448c2826eda7bf9a46cfb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T13:41:35Z |
| publishDate | 2021-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-f1fe39e7ef8448c2826eda7bf9a46cfb2022-12-21T22:59:26ZengNature PortfolioScientific Reports2045-23222021-07-0111111110.1038/s41598-021-94678-4Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP)Hamidreza Aboulkheyr Es0Hamid Mahdizadeh1Amir Abbas Hedayati Asl2Mehdi Totonchi3Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECRDepartment of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECRDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECRDepartment of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECRAbstract Carcinoma of Unknown Primary (CUP) is a heterogeneous and metastatic disease where the primary site of origin is undetectable. Currently, chemotherapy is the only state-of-art treatment option for CUP patients. The molecular profiling of the tumour, particularly mutation detection, offers a new treatment approach for CUP in a personalized fashion using targeted agents. We analyzed the mutation and copy number alterations profile of 1709 CUP samples deposited in the AACR Project Genomics Evidence Neoplasia Information Exchange (GENIE) cohort and explored potentially druggable mutations. We identified 52 significant mutated genes (SMGs) among CUP samples, in which 13 (25%) of SMGs were potentially targetable with either drugs are approved for the know primary tumour or undergoing clinical trials. The most variants detected were TP53 (43%), KRAS (19.90%), KMT2D (12.60%), and CDKN2A (10.30%). Additionally, using pan-cancer analysis, we found similar variants of TERT promoter in CUP and NSCLC samples, suggesting that these mutations may serve as a diagnostic marker for identifying the primary tumour in CUP. Taken together, the mutation profiling analysis of the CUP tumours may open a new way of identifying druggable targets and consequently administrating appropriate treatment in a personalized manner.https://doi.org/10.1038/s41598-021-94678-4 |
| spellingShingle | Hamidreza Aboulkheyr Es Hamid Mahdizadeh Amir Abbas Hedayati Asl Mehdi Totonchi Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP) Scientific Reports |
| title | Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP) |
| title_full | Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP) |
| title_fullStr | Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP) |
| title_full_unstemmed | Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP) |
| title_short | Genomic alterations and possible druggable mutations in carcinoma of unknown primary (CUP) |
| title_sort | genomic alterations and possible druggable mutations in carcinoma of unknown primary cup |
| url | https://doi.org/10.1038/s41598-021-94678-4 |
| work_keys_str_mv | AT hamidrezaaboulkheyres genomicalterationsandpossibledruggablemutationsincarcinomaofunknownprimarycup AT hamidmahdizadeh genomicalterationsandpossibledruggablemutationsincarcinomaofunknownprimarycup AT amirabbashedayatiasl genomicalterationsandpossibledruggablemutationsincarcinomaofunknownprimarycup AT mehditotonchi genomicalterationsandpossibledruggablemutationsincarcinomaofunknownprimarycup |